Abstract
Liprin-α4 was strongly induced following nickel (II) chloride exposure in a variety of cell types including BEAS-2B, A549, BEP2D and BL41 cells. Liprin-α4, a member of the Liprin alpha family, has seven isoforms but only three of these variants were detected in BEAS-2B cells (004, 201 and 202). The level of Liprin-α4 variants 201 and 004 were highly increased in BEAS-2B cells in response to nickel. We showed that Liprin-α4 bound directly to the cytoplasmic region of RPTP-LAR (receptor protein tyrosine phosphatase-leukocyte antigen-related receptor F). The cytoplasmic region of RPTP-LAR contains two phosphatase domains but only the first domain shows activity. The second domain interacts with other proteins. The phosphatase activity was increased both following nickel treatment and also in the presence of nickel ions in cell extracts. Liprin-α4 knock-down lines with decreased expression of Liprin-α4 variants 004 and 201 exhibited greater nickel toxicity compared to controls. The RPTP-LAR phosphatase activity was only slightly increased in a Liprin-α4 knock-down line. Liprin-α4 appeared necessary for the nickel induced tyrosine phosphatase activity. The presence of Liprin-α4 and nickel increased tyrosine phosphatase activity that reduced the global levels of tyrosine phosphorylation in the cell.
Highlights
The leucocyte common antigen-related (RPTP-LAR) protein is a member of the receptor protein tyrosine phosphatase (RPTP) F family that are single pass type I transmembrane receptor class 2A proteins [1,2]
RPTP-LAR plays a role in metabolic and cellular processes by its ability to respond to stimuli and transduce signals resulting in the regulation of biological processes
The Gene Chip array in BEAS-2B cells showed that Liprin-a4 was 3.7 fold upregulated after 24 h nickel exposure (Figure 1A) and Liprin-a4 mRNA was increased after nickel treatment in comparison to control), in a concentration dependent manner (Figure 1B)
Summary
The leucocyte common antigen-related (RPTP-LAR) protein is a member of the receptor protein tyrosine phosphatase (RPTP) F family that are single pass type I transmembrane receptor class 2A proteins [1,2]. RPTP-LAR contains an extracellular region with three immunoglobulin-like and eight fibronectin type III domains. The cytoplasmic region of the RPTP-LAR protein includes two protein tyrosine phosphatase (PTP) domains. Receptor type, F polypeptide (PTPRF), interacting protein alpha 1 (PPFIA1), known as Liprin-a1, was first identified as a binding protein of RPTP-LAR [5]. Liprin-a1 interacted with ING4, one of five protein members of the inhibitor of growth family [8]. The ING proteins are tumor suppressors of cancer invasion and metastasis [9,10]
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